Harnessing the regenerative potential of the central nervous system to repopulate depleted cellular populations from endogenous stem cells would be a novel approach for the treatment of neurological diseases resulting from cell death. Consequently, understanding if and how the central nervous system is capable of such regeneration would determine if such an approach is feasible. In this report, we provide evidence of widespread regenerative response in the spinal cord of amyotrophic lateral sclerosis transgenic mice. However, this regenerative response appears to be largely unproductive. We demonstrate that there is significantly increased gliogenesis, but an absence of convincing neurogenesis. The fact that the neurodegenerative process stimulates a regenerative response suggests that the adult spinal cord has at least limited ability for regeneration. Further studies will determine if this endogenous regenerative process can be enhanced and directed so as to slow or even reverse the natural progression of this devastating disease.